Pathological Findings in Congenital Diaphragmatic Hernia on necropsy
studies: A Single-Center Case Series
Chu-Yi Meng1, Ji-Zhen Zou3, Ying Wang2, Yan-Dong Wei2, Jing-Na Li2, Chao Liu2,
Zhong Feng2, Ling-Ling Cai3, Ping Xiao3, Li-Shang Ma*1,2
Affiliation
1Department of Neonatal Surgery, Children’s Hospital of Capital Institute of Pediatrics, Beijing, China.
2Department of Neonatal Surgery, Children’s Hospital of Capital Institute of Pediatrics, Graduate School of Peking Union Medical College, Beijing, China.
3Department of Pathology, Children’s Hospital of Capital Institute of Pediatrics, Beijing, China.
*Correspondence to
Dr Li-Shuang Ma, Department of Neonatal Surgery, Children’s Hospital of Capital Institute of Pediatrics, Graduate School of Peking Union Medical College, Beijing, China;malishuang2006@126.com
Funding Information:
This work was supported by the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority(XTZD20180305);Foundation project of Beijing Research Association for Chronic Disease Prevention and Health Education in 2022(BJMB0012022028001)
* Chu-Yi Meng and Ji-Zhen Zou contributed equally to this article.
Abstract
Introduction: Congenital diaphragmatic hernia (CDH) is known with high mortality rates and significant pulmonary morbidities. The objective of this study was to describe the histopathological findings of necropsy and clinical manifestations in CDH patients to find the clinicopathological correlations.
Methods: We reviewed the postmortem findings with associated clinical characteristics retrospectively in 8 CDH cases from 2017 to2022 July.
Results: Of the eight cases, one was bilateral congenital eventration diagnosed by autopsy. Severe pulmonary hypertension with a right to left shunting of large patent ductus arteriosus (PDA) obtained from echocardiogram were most common. And the average time of survive was 46 (8-624) h. According to the autopsy reports, the major pathological lung changes were diffuse alveolar damages (congestion and hemorrhage) and hyaline membrane formation. Notably, although the lung volume was significantly reduced, pulmonary structural dysplasia was not observed at all, presented normal lung development (50%); bilateral (25%) or ipsilateral (25%). Lobulated deformities were accompanied in three (37.5%) cases. All patients exhibited large PDA and a patent foramen ovale with increased right ventricle (RV) volume, and the myocardial fibers were slightly congested and swollen. Pulmonary vessels showed mild to moderate arterial media thickening. Lung hypoplasia and diffuse lung damages reduced gas exchange, meanwhile the PDA and PH caused RV failure, contributed a clinical picture of organ dysfunction, which lead to death.
Conclusions: Pulmonary structures have certain heterogeneity in CDH. The arteries’ pathological changes are not consistent with clinical diagnosis. And the adverse outcome may should be due to the cardiopulmonary vicious cycle.
Keyword: Congenital Diaphragmatic Hernia; Postmortem Examination; Pulmonary Hypoplasia; Pulmonary Hypertension.
1.INTRODUCTION
Congenital diaphragmatic hernia (CDH) is a serious life-threatening malformation, with an incidence of per 2.3 in 10,000 births1, characterized by abdominal visceral herniation into the chest. Infants with CDH are born with a variable degrees of lung hypoplasia and abnormal pulmonary vasculature, leading to ventilatory insufficiency and pulmonary hypertension (PH)2. During the last decades, survival of CDH patients has improved significantly due to the advances in neonatal intensive care and minimally invasive surgery technologies, however there are still 30-50% patients dying of fatal physiological changes3. The optimal managements of severe CDH remain challenging. Undoubtedly, severity of pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction are major determinants of CDH outcome4, 5.
CDH can differ in size and location, the most common type are posterolateral defects (Bochdalek hernia), presented in 70%-75% of cases; Anterior defects (Morgagni hernia) present in 23%-28%; and central hernias (2%-3%) are less frequent. Congenital eventration, characterized by incomplete formation of the diaphragm musculature, occurs in different parts of the diaphragm, and does not include communication between the peritoneal and thoracic cavities6,7. While diaphragm eventration is certainly a less common phenotype of CDH which often misdiagnosed. Bochdalek hernias occur mostly on the left side, however defects on the right side and bilateral indicate a higher mortality8. The pathogenesis of CDH is multifactorial and its epidemiology is poorly understood9. Cardiopulmonary pathophysiological processes in CDH patients are still ambiguous; in addition, the permissions of autopsy have continued to decrease in recent decades, and human tissue samples for translational and molecular studies of CDH are rarely available10. Postmortem investigation helps to identify the cause of death, as well as to explore the pathogenesis of the disease based on human. Therefore, in this literature, we performed few comprehensive autopsies of infants with CDH under the permission of parents in our center, observed their pathological changes and clinical characteristics, moreover, it is helpful to establish a biobank to promote the translational study of CDH.
2.MATERIALS AND METHODS
Ethical approval (SHERLLM2022036) was obtained from the Health Research Ethics Board of Children ’s Hospital, Capital Institute of Pediatrics. Infants with CDH who were admitted to the intensive care unit between 2017 and 2022 July and died on initial admission at the Department of Neonatal Surgery were included. With the informed consent of the parents, a comprehensive autopsy was assessed by pediatric pathologists in the Department of Pathology of our hospital. All bodies were placed at 4 °C until the autopsy was performed and maximum time from death to autopsy was 2 days postmortem. Paraffin blocks were retrieved from main organs and tissues of the body, stained with hematoxylin and eosin (HE) in 5μm thick sections, were also stained with antibodies against TTF-1 and alpha‐smooth muscle actin (HHF35) to better characterize pulmonary epithelial cells and artery muscularization. The relevant clinical diagnosis and treatment data derived from medical records were obtained.
The clinical data of CDH cases were retrospectively collected, including gender, gestational age (GA) at diagnosis, GA in birth, birth weight (BW), mode of delivery, side of hernia, liver herniation, defect size (A, B, C, D) as used by the Congenital Diaphragmatic Hernia Study Group (CDHSG) grade, and length of stay; disease-related information included pulmonary hypertension (PH) (first cardiac ultrasound examination after birth), cardiac anomalies; therapeutic interventions of PH, and repair surgery.
3.RESULTS
The results of clinical data and autopsy reports with CDH are presented in Table 1 and Table 2. Of the 8 patients (males=4, females=4), there were 2(20%) cases of left diaphragmatic hernia, 5(62.5%) cases of right and 1(12.5%) case misdiagnosed as left diaphragmatic hernia, confirmed as bilateral congenital eventration at autopsy; 3 cases (37.5%) of postoperative death and 5(62.5%) were failed to reach preoperative steady state and died. The median GA at birth was 37.5 (range, 29-39, IQR 34.75-38.75) weeks and median GA in diagnosis was 22 (range, 22- 28, IQR 22-24.75) weeks; There were 7(87.5%) cesarean sections and 1(12.5%) spontaneous delivery; the average birth weight was 3006.25g ± 1017.85g; the average time of survive was 127.63h ± 205.62h (range, 8-624) h; defect size by CDHSG were divided into D (57.1%)and C(42.9%), all of which had herniation of the liver significantly. The degree of pulmonary hypertension was all recognized as severe with a right-to-left shunt; Cardiac anomalies such as large patent ductus arteriosus (PDA) and patent foramen ovale (PFO) were diagnosed by echocardiography. After birth, 7 patients (85.7%) received high-frequency ventilator-assisted ventilation (HFOV), with a median initial mean airway pressure (MAP) of 14 (range, 14-22) cmH2O and up to 18 (range, 16-22) cmH2O finally. One received ECMO. Inotropic therapy was used to stabilize blood pressure and maintain systemic pressure. All patients were treated with vasoactive drugs including inhaled nitric oxide (iNO) and Sildenafil.
Complications included left ventricular (LV) dysplasia (1/8), pulmonary hemorrhage (3/8), pneumothorax (3/8), scoliosis (1/8), and oliguria (2/8). Due to persistent pulmonary hypertension of newborn (PPHN) at last, patients died for severe refractory hypoxemia, cardiopulmonary failure, uncorrectable decompensated mixed acidosis, and multiple organ failure.
Table 1. Demographics and characteristics of CDH Patients